The effort to find new treatments for humans with obsessive compulsive disorder receives a major boost with the development of mice that go bald and develop sores as a result of obsessive grooming, and are too timid to venture out of the corner of their cages.

The symptoms of the genetically altered mice were reversed with antidepressants, notably Prozac, and genetic targeting of a key brain circuit in a study that suggests new strategies for treating the debilitating psychiatric disorder, which is thought to affect up to three people in every 100 with obsessions, compulsions and stress

Researchers bred the mice to lack a specific gene, one responsible for the manufacture in the brain of a protein. This triggered defects in a brain circuit previously implicated in the disease and, after a few months, symptoms of the disorder.

Much like people with the illness, the mice engaged in compulsive grooming, which led to bald patches with open sores and bleeding. They also have abnormal firing of circuits in part of the brain called the striatum, one of the brain's information processing and decision-making centres.

Although the striatum has been implicated before in the disease, the team is now able to pinpoint the affected circuit for the first time, a boon for those developing treatments.

"The mice that could not produce this protein exhibited behaviours similar to that of humans with OCD, a compulsive action coupled with increased anxiety," said the lead researcher, Prof Guoping Feng of Duke University, whose team's work is reported today in the journal Nature.

"We obviously cannot talk to mice to find out what they are thinking, but these mutant mice clearly did things that looked like OCD."

Videotapes confirmed that the sores were self-inflicted - grooming behaviour gone amok. "We were surprised by the magnitude of this phenomenon," said Prof Feng. Now the team is studying OCD patients to see if they have a faulty or missing version of the gene.

When the missing gene was reinserted into the affected brain circuit of the mice, both the obsessive grooming and the defects were largely prevented. And the mice were made better by drugs called selective serotonin reuptake inhibitors, (such as Prozac) the class of drugs frequently used to treat OCD in patients.

This suggests that this mouse model will provide new means for testing theories of the precise molecular cause and, in turn, help improve the treatments for OCD.

The gene, SAPAP3, makes a protein that helps brain cells communicate with each other using the chemical glutamate, one that was not thought to be involved in the disease until now but is present in significant amounts in the striatum.

Because of its newly recognised role, "it may lead to new targets for drug development," explained Prof Feng. "An imbalance in SAPAP3 gene-related circuitry could help explain OCD."

Because drugs that affect glutamate in the brain are already under development for the treatment of some other neurological disorders, they may find other uses in combating OCD.

"This serendipitous discovery illustrates how pursuit of basic science questions can provide important insights with promising clinical implications into poorly understood diseases," said the director of the US National Institute of Neurological Disorders and Stroke, Dr Story Landis.

"Ultimately, the challenge will be to translate what we learn from this stunning new genetic animal model into help for the 2.2 million American adults haunted by unwanted thoughts and repetitive behaviours," added the director of the US National Institute of Mental Health, Dr Thomas Insel.

The team is looking beyond the SAPAP3 gene to other related genes of hundreds involved in the circuit that could lead to similar behavioural problems.

They are exploring how the SAPAP3 gene affects neural communications and how it works at the molecular level - with an eye to drug development.

Fellow investigators are exploring whether variants of the SAPAP3 gene in humans may be related to related disorders, such as trichotillomania, or obsessive hair pulling.